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公开(公告)号：US20070083006A1
公开(公告)日：2007-04-12
申请号：US10553570
申请日：2004-04-08
申请人： Kenneth Hinds , Danny Lewis , Paul Schmidt , Kathleen Campell
发明人： Kenneth Hinds , Danny Lewis , Paul Schmidt , Kathleen Campell
CPC分类号： A61K47/60 , A61K9/5031 , A61K38/28 , C07K14/62
摘要： The invention is directed to a single-step method for rapidly and efficiently preparing protein-polymer conjugates, including an insulin-polymer conjugate. According to the method of the present invention, a protein and hydrophilic polymer are contacted in the presence of at least one organic solvent and at least one metal chelator, under conditions that promote the formation of a conjugate of the protein and polymer. Thus, the invention is directed to the site-specific modification of selected proteins, such as insulin, with poly(ethylene glycol) at residue PheB 1. The invention also provides a pharmaceutical formulation for encapsulating the conjugate in a biodegradable polymer.
摘要翻译： 本发明涉及用于快速且有效地制备包括胰岛素 - 聚合物缀合物的蛋白质 - 聚合物缀合物的单步方法。 根据本发明的方法，蛋白质和亲水性聚合物在至少一种有机溶剂和至少一种金属螯合剂的存在下，在促进蛋白质和聚合物的缀合物形成的条件下接触。 因此，本发明涉及在残基PheB 1上与聚（乙二醇）一起选择的蛋白质（例如胰岛素）的位点特异性修饰。本发明还提供用于将缀合物包封在可生物降解的聚合物中的药物制剂。
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公开(公告)号：US09040664B2
公开(公告)日：2015-05-26
申请号：US10553570
申请日：2004-04-08
申请人： Kenneth Hinds , Danny Lewis , Paul Schmidt , Kathleen M. Campbell
发明人： Kenneth Hinds , Danny Lewis , Paul Schmidt , Kathleen M. Campbell
CPC分类号： A61K47/60 , A61K9/5031 , A61K38/28 , C07K14/62
摘要： The invention is directed to a single-step method for rapidly and efficiently preparing protein-polymer conjugates, including an insulin-polymer conjugate. According to the method of the present invention, a protein and hydrophilic polymer are contacted in the presence of at least one organic solvent and at least one metal chelator, under conditions that promote the formation of a conjugate of the protein and polymer. Thus, the invention is directed to the site-specific modification of selected proteins, such as insulin, with poly(ethylene glycol) at residue PheB1. The invention also provides a pharmaceutical formulation for encapsulating the conjugate in a biodegradable polymer.
摘要翻译： 本发明涉及用于快速且有效地制备包括胰岛素 - 聚合物缀合物的蛋白质 - 聚合物缀合物的单步方法。 根据本发明的方法，蛋白质和亲水性聚合物在至少一种有机溶剂和至少一种金属螯合剂的存在下，在促进蛋白质和聚合物的缀合物形成的条件下接触。 因此，本发明涉及在残基PheB1上的聚（乙二醇）选择的蛋白质如胰岛素的位点特异性修饰。 本发明还提供了用于将缀合物包封在可生物降解的聚合物中的药物制剂。
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3.发明申请公开(公告)号：US20080292712A1
公开(公告)日：2008-11-27
申请号：US12186203
申请日：2008-08-05
申请人： Danny Lewis , Paul Schmidt , Kenneth Hinds
发明人： Danny Lewis , Paul Schmidt , Kenneth Hinds
CPC分类号： A61K47/6927 , A61K47/593 , A61K47/60 , A61K47/61
摘要： Formulations for controlled, prolonged release of bioactive molecules such as therapeutic proteins, peptides and oligonucleotides have been developed. These formulations are based on solid microparticles or nanoparticles formed of the combination of biodegradable, synthetic polymers such as poly (lactic acid) (PLA), poly (glycolic acid) (PGA), and copolymers thereof. Bioactive molecules are coupled to hydrophilic polymers such as polyethylene glycol or polypropylene glycol and formulated to provide controlled release. The bioactive molecules are more stable, less immunogenic and have improved release rate profiles with lower burst levels and increased drug loading relative to the same bioactive molecules lacking coupled hydrophilic polymers. The controlled release formulations can be administered by injection, by inhalation, nasally, or orally.
摘要翻译： 已经开发了用于受控的，延长释放生物活性分子例如治疗性蛋白质，肽和寡核苷酸的制剂。 这些制剂基于由可生物降解的合成聚合物如聚（乳酸）（PLA），聚（乙醇酸）（PGA）及其共聚物的组合形成的固体微粒或纳米颗粒。 将生物活性分子偶联到亲水性聚合物如聚乙二醇或聚丙二醇上，并配制成提供受控释放。 相对于缺乏偶联亲水聚合物的相同生物活性分子，生物活性分子更稳定，免疫原性更小，具有更低的爆发水平和更高的药物负载量的改善的释放速率分布。 控制释放制剂可以通过注射，吸入，鼻腔或口服给药。
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4.发明授权公开(公告)号：US06706289B2
公开(公告)日：2004-03-16
申请号：US09999820
申请日：2001-10-31
申请人： Danny Lewis , Paul Schmidt , Kenneth Hinds
发明人： Danny Lewis , Paul Schmidt , Kenneth Hinds
IPC分类号： A61F202
CPC分类号： A61K47/6927 , A61K47/593 , A61K47/60 , A61K47/61
摘要： Formulations for controlled, prolonged release of bioactive molecules such as therapeutic proteins, peptides and oligonucleotides have been developed. These formulations are based on solid microparticles or nanoparticles formed of the combination of biodegradable, synthetic polymers such as poly(lactic acid) (PLA), poly(glycolic acid) (PGA), and copolymers thereof. Bioactive molecules are coupled to hydrophilic polymers such as polyethylene glycol or polypropylene glycol and formulated to provide controlled release. The bioactive molecules are more stable, less immunogenic and have improved release rate profiles with lower burst levels and increased drug loading relative to the same bioactive molecules lacking coupled hydrophilic polymers. The controlled release formulations can be administered by injection, by inhalation, nasally, or orally.
摘要翻译： 已经开发了用于受控的，延长释放生物活性分子例如治疗性蛋白质，肽和寡核苷酸的制剂。 这些制剂基于由可生物降解的合成聚合物如聚（乳酸）（PLA），聚（乙醇酸）（PGA）及其共聚物的组合形成的固体微粒或纳米颗粒。 将生物活性分子偶联到亲水性聚合物如聚乙二醇或聚丙二醇上，并配制成提供受控释放。 相对于缺乏偶联亲水聚合物的相同生物活性分子，生物活性分子更稳定，免疫原性更小，具有更低的爆发水平和更高的药物负载量的改善的释放速率分布。 控制释放制剂可以通过注射，吸入，鼻腔或口服给药。
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